Clinical value of in vitro tests for the management of severe drug hypersensitivity reactions

The role of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in neurosurgical practice is a secondary one, however they are still constantly involved in perioperative management of pain or in nonoperative management of acute radiculopathy. Beside the well-known adverse reactions (ADRs), the neurosurgeon practitioner should also take in account the drug hypersensitivity reactions (DHRs) of NSAIDs and be able to deal with it. The aim of this paper was to review the diagnostic and management steps for NSAIDs-induced Hypersensitivity Reactions. The actual stratification of NSAIDs-induced Hypersensitivity Reactions is based on understanding of the heterogeneity of immunological/non-immunological mechanisms of reactions and complexity of clinical manifestations. Practically, this stratification allows the physician to assess suspicion of DHR, based on anamnesis and clinical analysis, and to consider further practical steps to manage and eventually confirm the diagnosis. Drug allergies are considered only the DHRs for which a definite immunological mechanism (either drug-specific antibody or T cell) is demonstrated. In conclusion, clinical analysis and anamnesis of patient with NSAIDs-induced Hypersensitivity Reactions can be realized by any physician and could be enough to diagnose, but it is not sufficient to confirm the diagnosis. In vitro tests and oral provocation challenges may be necessary to be undertaken by an allergy specialist.

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In-Vitro Approaches to Predict and Study T-Cell Mediated Hypersensitivity to Drugs

Frontiers in Immunology ◽

10.3389/fimmu.2021.630530 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sean Hammond ◽

Paul Thomson ◽

Xiaoli Meng ◽

Dean Naisbitt

Keyword(s):

Chemical Reactivity ◽

Drug Hypersensitivity ◽

Poor Performance ◽

Preclinical Studies ◽

Hypersensitivity Reactions ◽

Clinical Use ◽

Lead Compound ◽

Drug Hypersensitivity Reactions ◽

Compound Selection

Mitigating the risk of drug hypersensitivity reactions is an important facet of a given pharmaceutical, with poor performance in this area of safety often leading to warnings, restrictions and withdrawals. In the last 50 years, efforts to diagnose, manage, and circumvent these obscure, iatrogenic diseases have resulted in the development of assays at all stages of a drugs lifespan. Indeed, this begins with intelligent lead compound selection/design to minimize the existence of deleterious chemical reactivity through exclusion of ominous structural moieties. Preclinical studies then investigate how compounds interact with biological systems, with emphasis placed on modeling immunological/toxicological liabilities. During clinical use, competent and accurate diagnoses are sought to effectively manage patients with such ailments, and pharmacovigilance datasets can be used for stratification of patient populations in order to optimise safety profiles. Herein, an overview of some of the in-vitro approaches to predict intrinsic immunogenicity of drugs and diagnose culprit drugs in allergic patients after exposure is detailed, with current perspectives and opportunities provided.

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Evaluation of a human in vitro skin test for predicting drug hypersensitivity reactions

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2019.02.005 ◽

2019 ◽

Vol 369 ◽

pp. 39-48 ◽

Cited By ~ 5

Author(s):

S.S. Ahmed ◽

J. Whritenour ◽

M.M. Ahmed ◽

L. Bibby ◽

L. Darby ◽

...

Keyword(s):

Skin Test ◽

Drug Hypersensitivity ◽

Hypersensitivity Reactions ◽

Drug Hypersensitivity Reactions

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In Vitro and In Vivo Tests for Drug Hypersensitivity Reactions

Drug Allergy Testing ◽

10.1016/b978-0-323-48551-7.00008-0 ◽

2018 ◽

pp. 85-95

Author(s):

Justin Greiwe ◽

Jonathan A. Bernstein

Keyword(s):

Drug Hypersensitivity ◽

Hypersensitivity Reactions ◽

In Vivo Tests ◽

Drug Hypersensitivity Reactions

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Skin testing and drug challenge in the evaluation of drug hypersensitivity reactions

Allergy and Asthma Proceedings ◽

10.2500/aap.2021.42.200091 ◽

2021 ◽

Vol 42 (1) ◽

pp. 16-21 ◽

Cited By ~ 1

Author(s):

Anna R. Wolfson ◽

Aleena Banerji

Keyword(s):

Negative Impact ◽

Skin Testing ◽

Drug Hypersensitivity ◽

Clinical History ◽

Hypersensitivity Reactions ◽

Causative Drug ◽

Care Assessment ◽

Drug Hypersensitivity Reactions ◽

Drug Challenge ◽

Drug Challenges

Immediate hypersensitivity to drugs is characterized by symptoms such as hives, swelling, and wheezing. To prevent a negative impact on care, assessment by an allergist is important. Evaluation requires a clear clinical history, but it is often lacking or vague, which makes a diagnosis difficult. Allergists instead can use skin testing and drug challenge to evaluate drug hypersensitivity reactions, which help the patient and provider understand the causative drug(s) and, more importantly, enables the use of the exonerated drug(s). Although penicillin skin testing is standardized, well described, and widely used, skin testing for most other drugs requires the use of a nonirritating skin testing concentration that can have a low negative predictive value. Drug challenges are the criterion standard for confirming tolerance. The allergist must obtain an in-depth clinical history and then follow with skin testing and/or drug challenges when indicated to determine which drugs can be de-labelled and which should be avoided. In this review, we focused on the evaluation of drug hypersensitivity reactions to antibiotics, perioperative agents, biologics, and chemotherapeutics.

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Severe Drug Hypersensitivity Reactions: Clinical Pattern, Diagnosis, Etiology and Therapeutic Options

Current Pharmaceutical Design ◽

10.2174/1381612822666160928125152 ◽

2017 ◽

Vol 22 (45) ◽

pp. 6852-6861 ◽

Cited By ~ 16

Author(s):

Maren Paulmann ◽

Maja Mockenhaupt

Keyword(s):

Drug Hypersensitivity ◽

Therapeutic Options ◽

Hypersensitivity Reactions ◽

Clinical Pattern ◽

Drug Hypersensitivity Reactions ◽

Pattern Diagnosis

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Clinical Phenotypes of Severe Cutaneous Drug Hypersensitivity Reactions

Current Pharmaceutical Design ◽

10.2174/1381612825666191107162921 ◽

2019 ◽

Vol 25 (36) ◽

pp. 3840-3854 ◽

Cited By ~ 2

Author(s):

Hakan Guvenir ◽

Tugba Arikoglu ◽

Emine Vezir ◽

Emine Dibek Misirlioglu

Keyword(s):

Adverse Drug Reactions ◽

Drug Hypersensitivity ◽

Stevens Johnson Syndrome ◽

Facial Oedema ◽

Hypersensitivity Reactions ◽

Drug Reactions ◽

Cutaneous Manifestations ◽

Clinical Phenotypes ◽

Drug Eruptions ◽

Drug Hypersensitivity Reactions

Drug hypersensitivity reactions are clinically heterogenous ranging from mild to severe. Most drug hypersensitivity reactions are accompanied by cutaneous manifestations. Fever, mucous membrane involvement, large blisters, facial oedema, pustulosis and visceral involvement are clinical features that lead to suspicion of severe adverse drug reactions. Severe cutaneous adverse drug reactions (SCARs) include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis. Serum sickness like reactions, drug induced vasculitis and generalized bullous fixed drug eruptions are less severe clinical entities. SCARs are uncommon but associated with significant morbidity and mortality. Physician should be aware of specific red flags and danger signs to immediately identify these reactions. Immediate drug withdrawal is mandatory. Early diagnosis and appropriate treatment significantly affect the prognosis of the disease. The purpose of our review is to discuss clinical phenotypes of severe cutaneous drug hypersensitivity reactions.

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